Salient experiences are represented by unique transcriptional signatures in the mouse brain

Mukherjee, Diptendu; Ignatowska‐Jankowska, Bogna M.; Itskovits, Eyal; Gonzales, Ben J.; Turm, Hagit; Izakson, Liz; Haritan, Doron; Bleistein, Noa; Cohen, Chen; Amit, Ido; Shay, Tal; Grueter, Brad A.; Zaslaver, Alon; Citri, Ami

doi:10.7554/elife.31220

Cited by 37 publications

(59 citation statements)

References 46 publications

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“…How sequential gAPs may interact within a single cell is also unclear: do they summate, or might there be refractory phases? In some contexts, sustained repeated behaviors may sum to increase or prolong IEG expression, whereas in other contexts, sequential exposures to a stimulus can result in habituation of responses (23,24). Temporal interactions could emerge within individual cells (e.g., through epigenetic mechanisms; see below) or through systems-level modulations as originally outlined in 2000 (1).…”

Section: Gap In the Cell: Molecular Elementsmentioning

confidence: 99%

“…In behaving organisms, different experiences clearly trigger different patterns of genomic activation throughout the brain. This was demonstrated with formal rigor in the study of Mukherjee et al (24,28), where patterns of IEG expression in the mouse brain were compared across 13 different experiences, ranging from reinstatement of feeding and mild foot shock to different regiments of cocaine exposure and volitional sucrose consumption. Each experience was found to be represented by a unique transcriptional signature to the extent that a minimal expression profile of 4 IEGs across 7 brain regions was sufficient to decode an individual mouse's recent experience with nearly 100% accuracy.…”

Section: Gap Within Different Neural Contextsmentioning

confidence: 99%

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The role of the genome in experience-dependent plasticity: Extending the analogy of the genomic action potential

Clayton

Anreiter

Aristizabal

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Our past experiences shape our current and future behavior. These experiences must leave some enduring imprint on our brains, altering neural circuits that mediate behavior and contributing to our individual differences. As a framework for understanding how experiences might produce lasting changes in neural circuits, Clayton [D. F. Clayton, Neurobiol. Learn. Mem. 74, 185–216 (2000)] introduced the concept of the genomic action potential (gAP)—a structured genomic response in the brain to acute experience. Similar to the familiar electrophysiological action potential (eAP), the gAP also provides a means for integrating afferent patterns of activity but on a slower timescale and with longer-lasting effects. We revisit this concept in light of contemporary work on experience-dependent modification of neural circuits. We review the “Immediate Early Gene” (IEG) response, the starting point for understanding the gAP. We discuss evidence for its involvement in the encoding of experience to long-term memory across time and biological levels of organization ranging from individual cells to cell ensembles and whole organisms. We explore distinctions between memory encoding and homeostatic functions and consider the potential for perpetuation of the imprint of experience through epigenetic mechanisms. We describe a specific example of a gAP in humans linked to individual differences in the response to stress. Finally, we identify key objectives and new tools for continuing research in this area.

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Section: Gap In the Cell: Molecular Elementsmentioning

confidence: 99%

Section: Gap Within Different Neural Contextsmentioning

confidence: 99%

The role of the genome in experience-dependent plasticity: Extending the analogy of the genomic action potential

Clayton

Anreiter

Aristizabal

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…In the fruit fly, aggression or courtship behavior is controlled by a known subset of neurons and can be modified via cell‐specific splicing changes in the gene fruitless . Exposing mice to a variety of rewarding or aversive experiences induced unique expression responses of immediate early genes in different brain regions . These examples suggest that valence detection has a molecular component that has not yet been examined at the transcriptomic level.…”

Section: Introductionmentioning

confidence: 99%

Honey bee neurogenomic responses to affiliative and agonistic social interactions

Shpigler

Saul

Murdoch

et al. 2018

Genes Brain and Behavior

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Social interactions can be divided into two categories, affiliative and agonistic. How neurogenomic responses reflect these opposing valences is a central question in the biological embedding of experience. To address this question, we exposed honey bees to a queen larva, which evokes nursing, an affiliative alloparenting interaction, and measured the transcriptomic response of the mushroom body brain region at different times after exposure. Hundreds of genes were differentially expressed at distinct time points, revealing a dynamic temporal patterning of the response. Comparing these results to our previously published research on agonistic aggressive interactions, we found both shared and unique transcriptomic responses to each interaction. The commonly responding gene set was enriched for nuclear receptor signaling, the set specific to nursing was enriched for olfaction and neuron differentiation, and the set enriched for aggression was enriched for cytoskeleton, metabolism, and chromosome organization. Whole brain histone profiling after the affiliative interaction revealed few changes in chromatin accessibility, suggesting that the transcriptomic changes derive from already accessible areas of the genome. Although only one stimulus of each type was studied, we suggest that elements of the observed transcriptomic responses reflect molecular encoding of stimulus valence, thus priming individuals for future encounters. This hypothesis is supported by behavioral analyses showing that bees responding to either the affiliative or agonistic stimulus exhibited a higher probability of repeating the same behavior but a lower probability of performing the opposite behavior. These findings add to our understanding of the biological embedding at the molecular level.

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“…Activity-dependent gene expression profiles differ according to an animal's experience in a number of different brain areas, including the mPFC 28 , indicating that distinct events (i.e., fear memory retrieval vs. social interaction) can have unique experience-dependent "molecular signatures" 29 . The identification of transcriptomic signatures related to activation of spatially-localized neural circuits could compliment these findings by linking these circuits with defined behaviors at the molecular level.…”

Section: Molecular Signatures In the Vhc-prl Pathwaymentioning

confidence: 99%

Molecularly-Defined Hippocampal Inputs Regulate Population Dynamics in the Prelimbic Cortex to Suppress Context Fear Memory Recall

Hallock

Quillian

Maynard

et al. 2019

Preprint

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Associating fearful events with the context in which they occur is critical for survival. Dysregulation of contextfear memory processing is a hallmark symptom of several neuropsychiatric disorders, including generalized anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Both the hippocampus and prelimbic subregion (PrL) of the medial prefrontal cortex (mPFC) have been linked with context fear memory recall in rodents, but the mechanisms by which hippocampal-prelimbic circuitry regulates this process remains poorly understood. Spatial and genetic targeting of this circuit in mice allowed us to use molecular profiling to show that hippocampal neurons with projections to the PrL (vHC-PrL projectors) are a transcriptomically-distinct subpopulation that is enriched for expression of genes associated with both GAD and PTSD. We further show that stimulation of this population of vHC-PrL projectors suppresses context fear memory recall and impairs the ability of PrL neurons to dynamically distinguish between distinct phases of fear learning. Using transgenic and circuit-specific molecular targeting approaches, we demonstrate that unique patterns of activity-dependent gene transcription within vHC-PrL projectors causally regulate excitatory/inhibitory balance in the PrL during context fear memory recall. Together, our data illuminate the molecular mechanisms by which hippocampalprelimbic circuitry regulates the retrieval of contextually-mediated fear memories.

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Salient experiences are represented by unique transcriptional signatures in the mouse brain

Cited by 37 publications

References 46 publications

The role of the genome in experience-dependent plasticity: Extending the analogy of the genomic action potential

The role of the genome in experience-dependent plasticity: Extending the analogy of the genomic action potential

Honey bee neurogenomic responses to affiliative and agonistic social interactions

Molecularly-Defined Hippocampal Inputs Regulate Population Dynamics in the Prelimbic Cortex to Suppress Context Fear Memory Recall

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